CINALUKAST

Cysteinyl leukotriene (CysLT) receptors mediate a range of pro-inflammatory effects, such as constriction of airways and vascular smooth muscle, increased permeability of endothelial membranes leading to plasma exudation and edema, and enhanced secretion of viscous mucus. CysLT receptors have therefore been implicated in a range of inflammatory diseases, notably asthma.^1-3 There are at least two subtypes of CysLT leukotriene receptors, referred to as CysLT₁ and CysLT₂, and although there is some evidence for further subdivision, this remains to be confirmed.⁴ Sigma-RBI is pleased to be the first company to offer cinalukast (Ro 24-5913; Prod. No. C6239), a selective CysLT₁ leukotriene receptor antagonist.

Cinalukast:

• In vitro, competes with [³H]-LTD₄ binding to CysLT₁ leukotriene receptors in guinea-pig lung membranes, displaying an IC₅₀ value of 6.4 nM.⁴
• In vivo, dose-dependently inhibits bronchoconstriction induced by both the non-subtype selective CysLT agonist LTC₄ (Prod. No. L4886) and the CysLT₁ selective agonist LTD₄ (Prod. No. L5011) by i.v. (ID₅₀= 0.13 mg/kg), oral (ID₅₀= 0.12 mg/kg) and aerosol (IC₅₀= 0.008%) routes of administration.⁴
• Inhibits 100% of both LTC₄- and LTD₄- induced bronchoconstriction at a dose of 1 mg/kg.⁴
• In a single oral dose (10 mg/kg), produces a long-lasting inhibition of bronchoconstriction, with pharmacological effects being observed within 1 hour and maintained for up to 36 hrs.⁴

Physical Description   Off-white solid Solubility   Soluble in DMSO at 10 mg/ml. Insoluble in water. Molecular Formula   C23H28N2O3S Formula Weight   412.55 Sizes   5 mg; 25mg

References:

1. Figueroa, D.J., et al., Clin. Exp. Allergy, 33, 1380-1388 (2003).
2. Kawano, T., J. Allergy Clin. Immunol., 112, 369-374 (2003).
3. Hui, Y. and Funk, C.D., Biochem. Pharmacol., 64, 1549-1157 (2002).
4. O'Donnell, M., et al., J. Pharmacol. Exp. Ther., 259, 751-758 (1991).

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